HRP20150555T1 - Ethynyl derivatives as positive allosteric modulators of the mglur5 - Google Patents

Ethynyl derivatives as positive allosteric modulators of the mglur5 Download PDF

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HRP20150555T1
HRP20150555T1 HRP20150555TT HRP20150555T HRP20150555T1 HR P20150555 T1 HRP20150555 T1 HR P20150555T1 HR P20150555T T HRP20150555T T HR P20150555TT HR P20150555 T HRP20150555 T HR P20150555T HR P20150555 T1 HRP20150555 T1 HR P20150555T1
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pyridin
phenylethynyl
methyl
compound
alkyl
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Georg Jaeschke
Synese Jolidon
Lothar Lindemann
Heniz Stadler
Eric Vieira
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F. Hoffmann - La Roche Ag
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    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P70/00—Climate change mitigation technologies in the production process for final industrial or consumer products
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Claims (16)

1. Spoj, naznačen time, da ima sljedeću formulu I: [image] gdje X je N ili C-R, gdje R je vodik ili halogen; G je N ili CH; pod uvjetom da maksimalno jedan od G ili X može biti dušik; R1 je fenil ili piridinil, koji je prema potrebi supstituiran s halogenom; R2 je vodik, C1-4-alkil/ hidroksi, C1-4-alkoksi ili C(O)O-benzil; R3, R3',R4, R4', R6, R6' su međusobno neovisno vodik ili C1-4-alkil; ili R6 i R4 zajedno s atomom ugljika na kojega su priključeni, mogu tvoriti C4-6-cikloalkil-prsten, ako m je 0 i n je 1 ili 2; R5 je vodik ili C1-4-alkil; n je 0, 1 ili 2; m je 0 ili 1; pod uvjetom danim nisu istovremeno 0; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol, racemična smjesa, ili njegov odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.1. A compound characterized in that it has the following formula I: [image] where X is N or C-R, where R is hydrogen or halogen; G is N or CH; provided that at most one of G or X can be nitrogen; R 1 is phenyl or pyridinyl, optionally substituted with halogen; R 2 is hydrogen, C 1-4 -alkyl/hydroxy, C 1-4 -alkoxy or C(O)O-benzyl; R3, R3', R4, R4', R6, R6' are independently hydrogen or C1-4-alkyl; or R6 and R4, together with the carbon atom to which they are attached, can form a C4-6-cycloalkyl ring, if m is 0 and n is 1 or 2; R 5 is hydrogen or C 1-4 -alkyl; n is 0, 1 or 2; m is 0 or 1; under the given condition they are not simultaneously 0; or its pharmaceutically acceptable acid addition salt, racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 2. Spoj formule IA prema zahtjevu 1, naznačen time, da je ona sljedeća: [image] gdje R1 je fenil ili piridinil, koji je prema potrebi supstituiran s halogenom; R2 je vodik, C1-4-alkil, hidroksi, C1-4-alkoksi ili C(O)O-benzil; R4, R4', R6, R6' su međusobno neovisno vodik ili C1-4-alkil; ili R6 i R4 zajedno s atomom ugljika na kojega su priključeni, mogu tvoriti C4-6-cikloalkil-prsten; R5 je vodik ili C1-4-alkil; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol, racemična smjesa, ili njegov odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.2. The compound of formula IA according to claim 1, characterized in that it is the following: [image] where R 1 is phenyl or pyridinyl, optionally substituted with halogen; R2 is hydrogen, C1-4-alkyl, hydroxy, C1-4-alkoxy or C(O)O-benzyl; R4, R4', R6, R6' are mutually independently hydrogen or C1-4-alkyl; or R6 and R4, together with the carbon atom to which they are attached, can form a C4-6-cycloalkyl ring; R 5 is hydrogen or C 1-4 -alkyl; or its pharmaceutically acceptable acid addition salt, racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 3. Spoj formule IA prema bilo kojem od zahtjeva 1 ili 2, naznačen time, da su to sljedeći spojevi: (RS)-1,5,5-trimetil-3-(5-(femletinil)piridin-2-il)pirolidin-2-on, (RS)-1,5,5-trimetil-3-(5-(piridin-3-iletinil)piridin-2-il)pirolidin-2-on, (RS)-3-(5-((3-klorofenil)etinil)piridin-2-il)-1,5,5-trimetilpirolidin-2-on, (RS)-3-(5-((3-fluorofenil)etinil)piridin-2-il)-1,5,5-trimetilpirolidin-2-on, (RS)-3-hidroksi-1,5,5-trimetil-3-(5-(feniletinil)piridin-2-il)pirolidin-2-on, (RS)-3-metoksi-1,5,5-trimetil-3-(5-(feniletinil)piridin-2-il)pirolidin-2-on, (RS)-1,3,5,5-tetrametil-3-(5-(feniletinil)piridin-2-iI)pirolidin-2-on, (3RS,3aSR,6aSR)-1-metil-3-(5-feniletinil-piridin-2-il)-heksahidro-cikopenta[b]pirol-2-on, (3R,3aS,6aS) ili (3S,3aR,6aR)-1-metil-3-(5-feniletinil-piridin-2-il)-heksahidro-ciklopenta[b]pirol-2-on, (3RS,3aSR,6aSR)-3-[5-(4-fluoro-feniletinil)-piridin-2-il]-1-metil-heksahidro-ciklopenta[b]pirol-2-on, (3RS,3aSR,6aSR)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-heksahidro-ciklopenta[b]pirol-2-on, (3R,3aS,6aS) ili (3S,3aR,6aR)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-heksahidro-ciklopenta[b]pirol-2-on, (3S,3aR,6aR) ili (3R,3aS,6aS)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-heksahidro-ciklopenta[b]pirol-2-on, (3RS,6SR,7SR)-1-metil-3-(5-feniletinil-piridin-2-il)-oktahidro-indol-2-on, (3SR,6SR,7SR)-1-metil-3-(5-feniletinil-piridin-2-il)-oktahidro-indol-2-on, (3R,6S,7S)-1-metil-3-(5-feniletinil-piridin-2-il)-oktahidro-indol-2-on, i (3S,6R,7R)-1-metil-3-(5-feniletinil-piridin-2-il)-oktahidro-indol-2-on, (3RS,6SR,7SR)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-oktahidro-indol-2-on, (3SR,6SR,7SR)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-oktahidro-indol-2-on, (3R,6S,7S)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-oktahidro-indol-2-on, (3S,6R,7R)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-oktahidro-indol-2-on, (3R,6S,7S)-3-[5-(4-fluoro-feniletinil)-piridin-2-il]-1-metil-oktahidro-indol-2-on, (3S,6R,7R)-3-[5-(4-fluoro-feniletinil)-piridin-2-il]-1-metil-oktahidro-indol-2-on, (RS)-3-[5-(2-kloro-piridin-4-iletinil)-piridin-2-il]-1,5,5-trimetil-pirolidin-2-on, (S) ili (R)-3-[5-(2-kloro-piridin-4-iletinil)-piridin-2-il]-1,5,5-trimetil-pirolidin-2-on, ili (R) ili (S)-3-[5-(2-kloro-piridin-4-iletinil)-piridin-2-il]-1,5,5-trimetil-pirolidin-2-on.3. Compound of formula IA according to any one of claims 1 or 2, characterized in that they are the following compounds: (RS)-1,5,5-trimethyl-3-(5-(femlethynyl)pyridin-2-yl)pyrrolidin-2-one, (RS)-1,5,5-trimethyl-3-(5-(pyridin-3-ylethynyl)pyridin-2-yl)pyrrolidin-2-one, (RS)-3-(5-((3-chlorophenyl)ethynyl)pyridin-2-yl)-1,5,5-trimethylpyrrolidin-2-one, (RS)-3-(5-((3-fluorophenyl)ethynyl)pyridin-2-yl)-1,5,5-trimethylpyrrolidin-2-one, (RS)-3-hydroxy-1,5,5-trimethyl-3-(5-(phenylethynyl)pyridin-2-yl)pyrrolidin-2-one, (RS)-3-methoxy-1,5,5-trimethyl-3-(5-(phenylethynyl)pyridin-2-yl)pyrrolidin-2-one, (RS)-1,3,5,5-tetramethyl-3-(5-(phenylethynyl)pyridin-2-yl)pyrrolidin-2-one, (3RS,3aSR,6aSR)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-hexahydro-cyclopenta[b]pyrrol-2-one, (3R,3aS,6aS) or (3S,3aR,6aR)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-hexahydro-cyclopenta[b]pyrrol-2-one, (3RS,3aSR,6aSR)-3-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-hexahydro-cyclopenta[b]pyrrol-2-one, (3RS,3aSR,6aSR)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-hexahydro-cyclopenta[b]pyrrol-2-one, (3R,3aS,6aS) or (3S,3aR,6aR)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-hexahydro-cyclopenta[b]pyrrole-2- he, (3S,3aR,6aR) or (3R,3aS,6aS)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-hexahydro-cyclopenta[b]pyrrole-2- he, (3RS,6SR,7SR)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-octahydro-indol-2-one, (3SR,6SR,7SR)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-octahydro-indol-2-one, (3R,6S,7S)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-octahydro-indol-2-one, and (3S,6R,7R)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-octahydro-indol-2-one, (3RS,6SR,7SR)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-octahydro-indol-2-one, (3SR,6SR,7SR)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-octahydro-indol-2-one, (3R,6S,7S)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-octahydro-indol-2-one, (3S,6R,7R)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-octahydro-indol-2-one, (3R,6S,7S)-3-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-octahydro-indol-2-one, (3S,6R,7R)-3-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-octahydro-indol-2-one, (RS)-3-[5-(2-chloro-pyridin-4-ylethynyl)-pyridin-2-yl]-1,5,5-trimethyl-pyrrolidin-2-one, (S) or (R)-3-[5-(2-chloro-pyridin-4-ylethynyl)-pyridin-2-yl]-1,5,5-trimethyl-pyrrolidin-2-one, or (R) or (S)-3-[5-(2-chloro-pyridin-4-ylethynyl)-pyridin-2-yl]-1,5,5-trimethyl-pyrrolidin-2-one. 4. Spoj formule IB prema zahtjevu 1, naznačen time, da je ona sljedeća: [image] gdje X je N ili C-R, pri čemu R je halogen; R1 je fenil ili piridinil, koji je prema potrebi supstituiran s halogenom; R2 je vodik, C1-4-alkil, hidroksi, C1-4-alkoksi ili C(O)O-benzil; R4, R4', R6, R6' su međusobno neovisno vodik ili C1-4-alkil; ili R6 i R4 zajedno s atomom ugljika na kojega su priključeni, mogu tvoriti C4-6-cikloalkil-prsten; R5 je vodik ili C1-4-alkil; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol, racemična smjesa, ili njegov odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.4. The compound of formula IB according to claim 1, characterized in that it is the following: [image] where X is N or C-R, wherein R is halogen; R 1 is phenyl or pyridinyl, optionally substituted with halogen; R2 is hydrogen, C1-4-alkyl, hydroxy, C1-4-alkoxy or C(O)O-benzyl; R4, R4', R6, R6' are mutually independently hydrogen or C1-4-alkyl; or R6 and R4, together with the carbon atom to which they are attached, can form a C4-6-cycloalkyl ring; R 5 is hydrogen or C 1-4 -alkyl; or its pharmaceutically acceptable acid addition salt, racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 5. Spoj formule IB prema bilo kojem od zahtjeva 1 ili 4, naznačen time, da su to sljedeći spojevi: (RS)-benzil-1,5,5-trimetil-2-okso-(5-(feniletinil)pirimidin-2-il)pirolidin-3-karboksilat, (RS)-1,5,5-trimetil-3-(5-(feniletinil)pirimidin-2-il)pirolidin-2-on, (RS)-3-(5-((3-fluorofenil)etinil)pirimidin-2-il)-1,5,5-trimetilpirolidin-2-on, (RS)-3-(5-((4-fluorofenil)etinil)pirimidin-2-il)-1,5,5-trimetilpirolidin-2-on, ili (3RS,3aSR,6aSR)-1-metil-3-(5-feniletinil-pirimidin-2-il)-heksahidro-ciklopenta[b]pirol-2-on.5. Compound of formula IB according to any one of claims 1 or 4, characterized in that they are the following compounds: (RS)-benzyl-1,5,5-trimethyl-2-oxo-(5-(phenylethynyl)pyrimidin-2-yl)pyrrolidine-3-carboxylate, (RS)-1,5,5-trimethyl-3-(5-(phenylethynyl)pyrimidin-2-yl)pyrrolidin-2-one, (RS)-3-(5-((3-fluorophenyl)ethynyl)pyrimidin-2-yl)-1,5,5-trimethylpyrrolidin-2-one, (RS)-3-(5-((4-fluorophenyl)ethynyl)pyrimidin-2-yl)-1,5,5-trimethylpyrrolidin-2-one, or (3RS,3aSR,6aSR)-1-methyl-3-(5-phenylethynyl-pyrimidin-2-yl)-hexahydro-cyclopenta[b]pyrrol-2-one. 6. Spoj formule IC prema zahtjevu 1, naznačen time, da je ona sljedeća: [image] gdje R1 je fenil ili piridinil, koji je prema potrebi supstituiran s halogenom; R2 je vodik,C1-4-alkil, hidroksi, C1-4-alkoksi ili C(O)O-benzil; R4, R4', R6, R6' su međusobno neovisno vodik ili C1-4-alkil; ili R6 i R4 zajedno satom om ugljika na kojega su priključeni, mogu tvoriti C4-6-cikloalkil-prsten; R5 je vodik ili C1-4-alkil; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol, racemična smjesa, ili njegov odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.6. The compound of formula IC according to claim 1, characterized in that it is the following: [image] where R 1 is phenyl or pyridinyl, optionally substituted with halogen; R2 is hydrogen, C1-4-alkyl, hydroxy, C1-4-alkoxy or C(O)O-benzyl; R4, R4', R6, R6' are mutually independently hydrogen or C1-4-alkyl; or R 6 and R 4 together with the carbon to which they are attached, may form a C 4-6 cycloalkyl ring; R 5 is hydrogen or C 1-4 -alkyl; or its pharmaceutically acceptable acid addition salt, racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 7. Spoj formule IC prema bilo kojem od zahtjeva 1 ili 6, naznačen time, da su to sljedeći spojevi: (RS)-3-(6-((3-fluorofenil)etinil)piridazin-3-il)-1,5,5-trimetilpirolidin-2-on, (RS)-3-(6-((4-fluorofenil)etinil)piridazin-3-il)-1,5,5-trimetilpirolidin-2-on, ili (RS)-3-(6-(feniletinil)piridazin-3-il)-1,5,5-trimetilpirolidin-2-on.7. Compound of formula IC according to any one of claims 1 or 6, characterized in that they are the following compounds: (RS)-3-(6-((3-fluorophenyl)ethynyl)pyridazin-3-yl)-1,5,5-trimethylpyrrolidin-2-one, (RS)-3-(6-((4-fluorophenyl)ethynyl)pyridazin-3-yl)-1,5,5-trimethylpyrrolidin-2-one, or (RS)-3-(6-(phenylethynyl)pyridazin-3-yl)-1,5,5-trimethylpyrrolidin-2-one. 8. Spoj formule ID prema zahtjevu 1, naznačen time, da je ona sljedeća: [image] gdje R1 je fenil ili piridinil, koji je prema potrebi supstituiran s halogenom; R2 je vodik, C1-4-alkil, hidroksi, C1-4-alkoksi ili C(O)O-benzil; R3, R3', R4, R4', R6, R6' su međusobno neovisno vodik ili C1-4-alkil; R5 je vodik ili C1-4-alkil; n je 1 ili 2; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol, racemična smjesa, ili njegov odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.8. Compound of formula ID according to claim 1, characterized in that it is the following: [image] where R 1 is phenyl or pyridinyl, optionally substituted with halogen; R2 is hydrogen, C1-4-alkyl, hydroxy, C1-4-alkoxy or C(O)O-benzyl; R3, R3', R4, R4', R6, R6' are independently hydrogen or C1-4-alkyl; R 5 is hydrogen or C 1-4 -alkyl; n is 1 or 2; or its pharmaceutically acceptable acid addition salt, racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 9. Spoj formule ID prema bilo kojem od zahtjeva 1 ili 8, naznačen time, da su to sljedeći spojevi: (RS)-1,6,6-trimetil-3-(5-(feniletinil)piridin-2-il)piperidin-2-on, (RS)-3-(5-((3-fluorofenil)etinil)piridin-2-il)-1,6,6-trimetilpiperidin-2-on, (RS)-3-(5-((4-fluorofenil)etinil)piridin-2-il)-1,6,6-trimetilpiperidin-2-on, (RS)-1-metil-3-(5-(feniletinil-piridin-2-il)-azepan-2-on, (RS)-3-[5-(4-fluoro-feniletinil)-piridin-2-il]-1-metil-azepan-2-on, (RS)-3-[5-(3-fluoro-feniletinil)-piridin-2-il]-1-metil-azepan-2-on, (S ili R)-1-metil-3-(5-feniletinil-piridin-2-il)-azepan-2-on, ili (R ili S)-1-metil-3-(5-feniletinil-piridin-2-il)-azepan-2-on.9. The compound of formula ID according to any one of claims 1 or 8, characterized in that they are the following compounds: (RS)-1,6,6-trimethyl-3-(5-(phenylethynyl)pyridin-2-yl)piperidin-2-one, (RS)-3-(5-((3-fluorophenyl)ethynyl)pyridin-2-yl)-1,6,6-trimethylpiperidin-2-one, (RS)-3-(5-((4-fluorophenyl)ethynyl)pyridin-2-yl)-1,6,6-trimethylpiperidin-2-one, (RS)-1-methyl-3-(5-(phenylethynyl-pyridin-2-yl)-azepan-2-one, (RS)-3-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-azepan-2-one, (RS)-3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-1-methyl-azepan-2-one, (S or R)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-azepan-2-one, or (R or S)-1-methyl-3-(5-phenylethynyl-pyridin-2-yl)-azepan-2-one. 10. Spoj formule IE prema zahtjevu 1, naznačen time, da je ona sljedeća: [image] gdje R1 je fenil ili piridinil, koji je prema potrebi supstituiran s halogenom; R2 je vodik, C1-4-alkil, hidroksi, C1-4-alkoksi ili C(O)O-benzil; R3, R3', R4, R4', R6, R6' su međusobno neovisno vodik ili C1-4-alkil; R5 je vodik ili C1-4-alkil; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol, racemična smjesa, ili njegov odgovarajući enantiomer i/ili optički izomer i/ili stereoizomer.10. Compound of formula IE according to claim 1, characterized in that it is the following: [image] where R 1 is phenyl or pyridinyl, optionally substituted with halogen; R2 is hydrogen, C1-4-alkyl, hydroxy, C1-4-alkoxy or C(O)O-benzyl; R3, R3', R4, R4', R6, R6' are independently hydrogen or C1-4-alkyl; R 5 is hydrogen or C 1-4 -alkyl; or its pharmaceutically acceptable acid addition salt, racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 11. Spoj formule IE prema bilo kojem od zahtjeva 1 ili 10, naznačen time, da su to sljedeći spojevi: (RS)-1,6,6-trimetil-3-(5-(feniletinil)pirimidin-2-il)piperidin-2-on, (RS)-3-(5-((4-fluorofenil)etinil)pirimidin-2-il)-1,6,6-trimetilpiperidin-2-on, ili (RS)-3-(5-((3-fluorofenil)etinil)pirimidin-2-il)-1,6,6-trimetilpiperidin-2-on.11. A compound of formula IE according to any one of claims 1 or 10, characterized in that they are the following compounds: (RS)-1,6,6-trimethyl-3-(5-(phenylethynyl)pyrimidin-2-yl)piperidin-2-one, (RS)-3-(5-((4-fluorophenyl)ethynyl)pyrimidin-2-yl)-1,6,6-trimethylpiperidin-2-one, or (RS)-3-(5-((3-fluorophenyl)ethynyl)pyrimidin-2-yl)-1,6,6-trimethylpiperidin-2-one. 12. Postupak priprave spoja formule I prema bilo kojem od zahtjeva 1 do 11, naznačen time, da obuhvaća sljedeće varijante: a) reakcija spoja sljedeće formule 3: [image] gdje X1 je halogen, sa spojem sljedeće formule 4: [image] u tvorbu spoja formule I: [image] pri čemu su definicije opisane u zahtjevu 1, ili b) reakcija spoja sljedeće formule 5: [image] gdje X1 je halogen, sa spojem sljedeće formule 2: [image] za tvorbu spoja formule I: [image] pri čemu su definicije opisane u zahtjevu 1, ili ako se želi, pretvaranje dobivenih spojeva u farmaceutski prihvatljive kiselinske adicijske soli.12. The process for preparing the compound of formula I according to any one of claims 1 to 11, characterized in that it includes the following variants: a) reaction of the compound of the following formula 3: [image] where X1 is halogen, with a compound of the following formula 4: [image] in the formation of the compound of formula I: [image] wherein the definitions are described in claim 1, or b) reaction of the compound of the following formula 5: [image] where X1 is halogen, with a compound of the following formula 2: [image] for the formation of the compound of formula I: [image] where the definitions are described in claim 1, or if desired, converting the obtained compounds into pharmaceutically acceptable acid addition salts. 13. Spoj prema bilo kojem od zahtjeva 1 do 11, naznačen time, da se on upotrebljava kao terapeutski djelotvorna tvar.13. A compound according to any one of claims 1 to 11, characterized in that it is used as a therapeutically effective substance. 14. Farmaceutski sastav, naznačen time, da on obuhvaća spoj prema bilo kojem od zahtjeva 1 do 11 i terapeutski djelotvoran nosač.14. A pharmaceutical composition, characterized in that it comprises a compound according to any one of claims 1 to 11 and a therapeutically effective carrier. 15. Uporaba spoja prema bilo kojem od zahtjeva 1 do 11, naznačena time, da služi u proizvodnji lijeka za liječenje shizofrenije i kognitivnih bolesti.15. Use of the compound according to any one of claims 1 to 11, characterized in that it serves in the production of a drug for the treatment of schizophrenia and cognitive diseases. 16. Spoj prema bilo kojem od zahtjeva 1 do 11, naznačen time, da se on upotrebljava za liječenje shizofrenije i kognitivnih bolesti.16. The compound according to any one of claims 1 to 11, characterized in that it is used for the treatment of schizophrenia and cognitive diseases.
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